NM_000546.6(TP53):c.715A>G (p.Asn239Asp) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003137828.4

Allele description [Variation Report for NM_000546.6(TP53):c.715A>G (p.Asn239Asp)]

NM_000546.6(TP53):c.715A>G (p.Asn239Asp)

Gene:

TP53:tumor protein p53 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000546.6(TP53):c.715A>G (p.Asn239Asp)

HGVS:

NC_000017.11:g.7674248T>C
NG_017013.2:g.18303A>G
NM_000546.6:c.715A>GMANE SELECT
NM_001126112.3:c.715A>G
NM_001126113.3:c.715A>G
NM_001126114.3:c.715A>G
NM_001126115.2:c.319A>G
NM_001126116.2:c.319A>G
NM_001126117.2:c.319A>G
NM_001126118.2:c.598A>G
NM_001276695.3:c.598A>G
NM_001276696.3:c.598A>G
NM_001276697.3:c.238A>G
NM_001276698.3:c.238A>G
NM_001276699.3:c.238A>G
NM_001276760.3:c.598A>G
NM_001276761.3:c.598A>G
NP_000537.3:p.Asn239Asp
NP_000537.3:p.Asn239Asp
NP_001119584.1:p.Asn239Asp
NP_001119585.1:p.Asn239Asp
NP_001119586.1:p.Asn239Asp
NP_001119587.1:p.Asn107Asp
NP_001119588.1:p.Asn107Asp
NP_001119589.1:p.Asn107Asp
NP_001119590.1:p.Asn200Asp
NP_001263624.1:p.Asn200Asp
NP_001263625.1:p.Asn200Asp
NP_001263626.1:p.Asn80Asp
NP_001263627.1:p.Asn80Asp
NP_001263628.1:p.Asn80Asp
NP_001263689.1:p.Asn200Asp
NP_001263690.1:p.Asn200Asp
LRG_321t1:c.715A>G
LRG_321:g.18303A>G
LRG_321p1:p.Asn239Asp
NC_000017.10:g.7577566T>C
NM_000546.4:c.715A>G
NM_000546.5:c.715A>G
P04637:p.Asn239Asp

Protein change:

N107D

Links:

UniProtKB: P04637#VAR_045204; dbSNP: rs876660807

NCBI 1000 Genomes Browser:

rs876660807

Molecular consequence:

NM_000546.6:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.715A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.319A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.319A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.319A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.238A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.238A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.238A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.598A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003809655	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003936381	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jun 21, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003809655

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003936381

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Jun 21, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Revvity Omics, Revvity, SCV003809655.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV003936381.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate a damaging effect: non-functional transactivation and impaired growth suppression ability (Kato et al., 2003; Jordan et al., 2010; Kotler et al., 2018; Giacomelli et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with colorectal cancer, as well as an individual with breast and ovarian cancer who also harbored a BRCA1 variant (Yurgelun et al., 2017; Lerner-Ellis et al., 2021); This variant is associated with the following publications: (PMID: 9546439, 9635858, 9359923, 20407015, 26619011, 30840781, 15161705, 14559903, 12826609, 11793474, 30720243, 15510160, 30224644, 31105275, 32885271, 28135145, 29979965)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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